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XB-ART-45962
BMC Dev Biol December 17, 2012; 12 27.

Prolonged FGF signaling is necessary for lung and liver induction in Xenopus.



Abstract
FGF signaling plays numerous roles during organogenesis of the embryonic gut tube. Mouse explant studies suggest that different thresholds of FGF signaling from the cardiogenic mesoderm induce lung, liver, and pancreas lineages from the ventral foregut progenitor cells. The mechanisms that regulate FGF dose in vivo are unknown. Here we use Xenopus embryos to examine the hypothesis that a prolonged duration of FGF signaling from the mesoderm is required to induce foregut organs. We show that both mesoderm and FGF signaling are required for liver and lung development in Xenopus; formally demonstrating that this important step in organ induction is conserved with other vertebrate species. Prolonged contact with the mesoderm and persistent FGF signaling through both MEK and PI3K over an extended period of time are required for liver and lung specification. Inhibition of FGF signaling results in reduced liver and lung development, with a modest expansion of the pancreas/duodenum progenitor domain. Hyper-activation of FGF signaling has the opposite effect expanding liver and lung gene expression and repressing pancreatic markers. We show that FGF signaling is cell autonomously required in the endoderm and that a dominant negative FGF receptor decreases the ability of ventral foregut progenitor cells to contribute to the lung and liver buds. These results suggest that the liver and lungs are specified at progressively later times in development requiring mesoderm contact for different lengths of time. Our data suggest that this is achieved at least in part through prolonged FGF signaling. In addition to providing a foundation for further mechanistic studies on foregut organogenesis using the experimental advantages of the Xenopus system, these data have implications for the directed differentiation of stem cells into foregut lineages.

PubMed ID: 22988910
PMC ID: PMC3514138
Article link: BMC Dev Biol
Grant support: [+]
Genes referenced: akt1 fgf2 foxf1 gal.2 gjb1 hhex mapk1 nkx2-1 nkx2-5 nr1h5 pdx1 pik3ca ptf1a spry2 tnni3
Antibodies: Akt1 Ab1 Akt1 Ab4 H3f3a Ab2 Mapk1 Ab1 Mapk1 Ab6


Article Images: [+] show captions
References [+] :
Afelik, Combined ectopic expression of Pdx1 and Ptf1a/p48 results in the stable conversion of posterior endoderm into endocrine and exocrine pancreatic tissue. 2006, Pubmed, Xenbase


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